Environmental Genome Program ? Identification of Genes The human immunodeficiency virus (HIV) has successfully exploited crucial vulnerabilities in the immune system, and the search for biologic strategies to block the host-virus relationship requires knowledge of the fundamental mechanisms of interaction. HIV binding to immune cells requires binding of its gp120 surface protein to the CD4 and CCR5 receptors on the surface of immune cells as the key step for successful infection. Recent studies have shown individuals with the CCR5 deletion mutation are protected from viral infection. These genetic findings suggest alterations in the gene cascade required for HIV infection can greatly reduce the development of AIDS. Discovery of polymorphic variation in these genes will help both understanding the biochemical mechanism of the disease process, as well as suggest intervention strategies to interrupt the infection pathway. NIEHS is in the process of establishing cDNA microarray technology, and is developing chips with cDNA clone subarrays designed to determine the classes of genes which are expressed as a result of exposure to environmental agents. This technology is well suited for discovery of expressed and modulated genes as a consequence of HIV viral infection. The technology offers an potentially inexpensive, highly accurate and rapid method to investigate HIV related genes and the nature of mutations and polymorhpic variants